UniProtKB - O00327 (BMAL1_HUMAN)
Aryl hydrocarbon receptor nuclear translocator-like protein 1
ARNTL
Functioni
Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. ARNTL/BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART and KLF11. The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The NPAS2-ARNTL/BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence (PubMed:23229515).
CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTL binds to the half-site 5'-GTGA-3' (PubMed:23229515).
The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515).
Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (PubMed:28985504).
Plays a role in protecting against lethal sepsis by limiting the expression of immune checkpoint protein CD274 in macrophages in a PKM2-dependent manner (By similarity).
Regulates the diurnal rhythms of skeletal muscle metabolism via transcriptional activation of genes promoting triglyceride synthesis (DGAT2) and metabolic efficiency (COQ10B) (By similarity).
By similarity7 Publications(Microbial infection) Regulates SARS coronavirus-2/SARS-CoV-2 entry and replication in lung epithelial cells probably through the post-transcriptional regulation of ACE2 and interferon-stimulated gene expression.
1 PublicationMiscellaneous
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 125 | Important for interaction with CLOCK1 Publication | 1 |
GO - Molecular functioni
- aryl hydrocarbon receptor binding Source: BHF-UCL
- DNA binding Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: BHF-UCL
- DNA-binding transcription factor binding Source: GO_Central
- E-box binding Source: UniProtKB
- Hsp90 protein binding Source: BHF-UCL
- protein dimerization activity Source: InterPro
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: UniProtKB
- sequence-specific DNA binding Source: UniProtKB
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- circadian regulation of gene expression Source: UniProtKB
- circadian rhythm Source: GO_Central
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- negative regulation of fat cell differentiation Source: UniProtKB
- negative regulation of glucocorticoid receptor signaling pathway Source: UniProtKB
- negative regulation of TOR signaling Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- oxidative stress-induced premature senescence Source: UniProtKB
- positive regulation of canonical Wnt signaling pathway Source: UniProtKB
- positive regulation of circadian rhythm Source: ComplexPortal
- positive regulation of protein acetylation Source: UniProtKB
- positive regulation of skeletal muscle cell differentiation Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
- regulation of cell cycle Source: UniProtKB
- regulation of cellular senescence Source: UniProtKB
- regulation of hair cycle Source: UniProtKB
- regulation of insulin secretion Source: UniProtKB
- regulation of neurogenesis Source: UniProtKB
- regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- regulation of type B pancreatic cell development Source: UniProtKB
- response to redox state Source: UniProtKB
- spermatogenesis Source: UniProtKB
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | O00327 |
Reactomei | R-HSA-1368108, BMAL1:CLOCK,NPAS2 activates circadian gene expression R-HSA-1989781, PPARA activates gene expression R-HSA-400253, Circadian Clock R-HSA-9707616, Heme signaling |
SignaLinki | O00327 |
SIGNORi | O00327 |
Names & Taxonomyi
Protein namesi | Recommended name: Aryl hydrocarbon receptor nuclear translocator-like protein 1Alternative name(s): Basic-helix-loop-helix-PAS protein MOP3 Brain and muscle ARNT-like 1 Class E basic helix-loop-helix protein 5 Short name: bHLHe5 Member of PAS protein 3 PAS domain-containing protein 3 bHLH-PAS protein JAP3 |
Gene namesi | Name:ARNTL Synonyms:BHLHE5, BMAL1, MOP3, PASD3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:701, ARNTL |
MIMi | 602550, gene |
neXtProti | NX_O00327 |
VEuPathDBi | HostDB:ENSG00000133794 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
Note: Shuttles between the nucleus and the cytoplasm and this nucleocytoplasmic shuttling is essential for the nuclear accumulation of CLOCK, target gene transcription and the degradation of the CLOCK-ARNTL/BMAL1 heterodimer. The sumoylated form localizes in the PML body. Sequestered to the cytoplasm in the presence of ID2.By similarity
Nucleus
- CLOCK-BMAL transcription complex Source: ComplexPortal
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
- PML body Source: UniProtKB-SubCell
Other locations
- aryl hydrocarbon receptor complex Source: GO_Central
- chromatin Source: NTNU_SB
- chromatoid body Source: UniProtKB
- intracellular membrane-bounded organelle Source: HPA
- transcription regulator complex Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 9 | S → A or E: Enhanced PER1 reporter activity by CLOCK-ARNTL/BMAL1. 1 Publication | 1 | |
Mutagenesisi | 9 | S → F: 2-2.5-fold increase in CLOCK-BMAL1 transcriptional activity in the absence of CRY1. No change in repression activity in the presence of CRY1. 1 Publication | 1 | |
Mutagenesisi | 10 | S → A or E: Enhanced PER1 reporter activity by CLOCK-ARNTL/BMAL1. 1 Publication | 1 | |
Mutagenesisi | 10 | S → L: 2-2.5-fold increase in CLOCK-ARNTL/BMAL1 transcriptional activity in the absence of CRY1. No change in repression activity in the presence of CRY1. 1 Publication | 1 | |
Mutagenesisi | 78 | S → E: Phosphomimetic mutant which severely impairs DNA binding and CLOCK-ARNTL/BMAL1 transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 88 | M → F: No effect on CLOCK binding. 1 Publication | 1 | |
Mutagenesisi | 90 | S → E: Phosphomimetic mutant with no effect on DNA binding or CLOCK-ARNTL/BMAL1 transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 125 | L → H: Impaired CLOCK binding. 1 Publication | 1 | |
Mutagenesisi | 611 | A → S or T: Increased desensitization to CRY1, in the presence of CLOCK. Approximately 2-fold increase in CLOCK-ARNTL/BMAL1 transcriptional activity in the absence of CRY1; when associated with E-407. 1 Publication | 1 | |
Mutagenesisi | 612 | G → E: Increased desensitization to CRY1, in the presence of CLOCK. Approximately 2-fold increase in CLOCK-ARNTL/BMAL1 transcriptional activity in the absence of CRY1. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 406 |
OpenTargetsi | ENSG00000133794 |
PharmGKBi | PA24996 |
Miscellaneous databases
Pharosi | O00327, Tbio |
Genetic variation databases
BioMutai | ARNTL |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000127156 | 1 – 626 | Aryl hydrocarbon receptor nuclear translocator-like protein 1Add BLAST | 626 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 17 | Phosphoserine; by GSK3-betaBy similarity | 1 | |
Modified residuei | 21 | Phosphothreonine; by GSK3-betaBy similarity | 1 | |
Modified residuei | 78 | Phosphoserine1 Publication | 1 | |
Modified residuei | 90 | Phosphoserine; by CK2By similarity | 1 | |
Cross-linki | 252 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3)By similarity | ||
Cross-linki | 259 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 538 | N6-acetyllysineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | O00327 |
MassIVEi | O00327 |
MaxQBi | O00327 |
PaxDbi | O00327 |
PeptideAtlasi | O00327 |
PRIDEi | O00327 |
ProteomicsDBi | 47841 [O00327-2] 47842 [O00327-1] 47843 [O00327-3] 47844 [O00327-4] 47845 [O00327-5] 47846 [O00327-6] 47847 [O00327-7] 47848 [O00327-8] 47849 [O00327-9] |
PTM databases
GlyGeni | O00327, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O00327 |
PhosphoSitePlusi | O00327 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000133794, Expressed in left lobe of thyroid gland and 229 other tissues |
ExpressionAtlasi | O00327, baseline and differential |
Genevisiblei | O00327, HS |
Organism-specific databases
HPAi | ENSG00000133794, Low tissue specificity |
Interactioni
Subunit structurei
Component of the circadian clock oscillator which includes the CRY1/2 proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER1/2/3 proteins (By similarity).
Forms a heterodimer with CLOCK (PubMed:9616112, PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and ARNTL/BMAL1 (By similarity).
Part of a nuclear complex which also includes RACK1 and PRKCA; RACK1 and PRKCA are recruited to the complex in a circadian manner (By similarity).
Interacts with NPAS2 (By similarity).
Interacts with EZH2 (By similarity).
Interacts with SUMO3 (By similarity).
Interacts with SIRT1 (By similarity).
Interacts with AHR (PubMed:9079689).
Interacts with ID1, ID2 and ID3 (By similarity).
Interacts with DDX4 (By similarity).
Interacts with OGT (By similarity).
Interacts with EED and SUZ12 (By similarity).
Interacts with MTA1 (By similarity).
Interacts with CIART (PubMed:24385426).
Interacts with HSP90 (PubMed:9079689).
Interacts with KAT2B and EP300 (PubMed:14645221).
Interacts with BHLHE40/DEC1 and BHLHE41/DEC2 (By similarity).
Interacts with RELB and the interaction is enhanced in the presence of CLOCK (By similarity).
Interacts with PER1, PER2, CRY1 and CRY2 and this interaction requires a translocation to the nucleus (By similarity). Interaction of the CLOCK-ARNTL/BMAL1 heterodimer with PER or CRY inhibits transcription activation (By similarity). Interaction of the CLOCK-ARNTL/BMAL1 with CRY1 is independent of DNA but with PER2 is off DNA (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer interacts with GSK3B (By similarity).
Interacts with KDM5A (PubMed:21960634).
Interacts with KMT2A; in a circadian manner (By similarity).
Interacts with UBE3A (PubMed:24728990).
Interacts with PRKCG (By similarity).
Interacts with MAGEL2 (By similarity).
Interacts with NCOA2 (By similarity).
Interacts with THRAP3 (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer interacts with PASD1 (PubMed:25936801).
Interacts with PASD1 (PubMed:25936801).
Interacts with USP9X (PubMed:29626158).
Interacts with PIWIL2 (via PIWI domain) (PubMed:28903391).
Interacts with HDAC3 (By similarity).
Interacts with HNF4A (PubMed:30530698).
By similarity12 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 77 | Interaction with E-box DNA1 Publication | 1 | |
Sitei | 80 | Interaction with E-box DNA1 Publication | 1 | |
Sitei | 81 | Interaction with E-box DNA1 Publication | 1 | |
Sitei | 85 | Interaction with E-box DNA1 Publication | 1 |
Binary interactionsi
O00327
With | #Exp. | IntAct |
---|---|---|
CLOCK [O15516] | 4 | EBI-1794206,EBI-1794265 |
HIF1A [D0VY79] | 3 | EBI-1794206,EBI-10179332 |
Isoform 8 [O00327-8]
GO - Molecular functioni
- aryl hydrocarbon receptor binding Source: BHF-UCL
- DNA-binding transcription factor binding Source: GO_Central
- Hsp90 protein binding Source: BHF-UCL
- protein dimerization activity Source: InterPro
Protein-protein interaction databases
BioGRIDi | 106899, 99 interactors |
ComplexPortali | CPX-3229, CLOCK-BMAL1 transcription complex |
CORUMi | O00327 |
DIPi | DIP-46008N |
IntActi | O00327, 23 interactors |
MINTi | O00327 |
STRINGi | 9606.ENSP00000384517 |
Miscellaneous databases
RNActi | O00327, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O00327 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 72 – 125 | bHLHPROSITE-ProRule annotationAdd BLAST | 54 | |
Domaini | 143 – 215 | PAS 1PROSITE-ProRule annotationAdd BLAST | 73 | |
Domaini | 326 – 396 | PAS 2PROSITE-ProRule annotationAdd BLAST | 71 | |
Domaini | 401 – 444 | PACAdd BLAST | 44 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 60 | DisorderedSequence analysisAdd BLAST | 60 | |
Regioni | 458 – 493 | DisorderedSequence analysisAdd BLAST | 36 | |
Regioni | 508 – 588 | Interaction with CIARTBy similarityAdd BLAST | 81 | |
Regioni | 511 – 595 | DisorderedSequence analysisAdd BLAST | 85 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 36 – 41 | Nuclear localization signalBy similarity | 6 | |
Motifi | 142 – 152 | Nuclear export signal 1By similarityAdd BLAST | 11 | |
Motifi | 361 – 369 | Nuclear export signal 2By similarity | 9 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1 – 37 | Polar residuesSequence analysisAdd BLAST | 37 | |
Compositional biasi | 38 – 60 | Basic and acidic residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 512 – 532 | Polar residuesSequence analysisAdd BLAST | 21 | |
Compositional biasi | 548 – 574 | Polar residuesSequence analysisAdd BLAST | 27 |
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG3561, Eukaryota |
GeneTreei | ENSGT00940000157523 |
HOGENOMi | CLU_011864_2_2_1 |
InParanoidi | O00327 |
OMAi | YHHEDIP |
OrthoDBi | 331262at2759 |
PhylomeDBi | O00327 |
TreeFami | TF319983 |
Family and domain databases
CDDi | cd00130, PAS, 2 hits |
Gene3Di | 4.10.280.10, 1 hit |
IDEALi | IID00426 |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR001067, Nuc_translocat IPR001610, PAC IPR000014, PAS IPR035965, PAS-like_dom_sf IPR013767, PAS_fold |
Pfami | View protein in Pfam PF00010, HLH, 1 hit PF00989, PAS, 1 hit |
PRINTSi | PR00785, NCTRNSLOCATR |
SMARTi | View protein in SMART SM00353, HLH, 1 hit SM00086, PAC, 1 hit SM00091, PAS, 2 hits |
SUPFAMi | SSF47459, SSF47459, 1 hit SSF55785, SSF55785, 2 hits |
TIGRFAMsi | TIGR00229, sensory_box, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS50112, PAS, 2 hits |
s (9+)i Sequence
Sequence statusi: Complete.
This entry describes 9 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 9 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MADQRMDISS TISDFMSPGP TDLLSSSLGT SGVDCNRKRK GSSTDYQESM
60 70 80 90 100
DTDKDDPHGR LEYTEHQGRI KNAREAHSQI EKRRRDKMNS FIDELASLVP
110 120 130 140 150
TCNAMSRKLD KLTVLRMAVQ HMKTLRGATN PYTEANYKPT FLSDDELKHL
160 170 180 190 200
ILRAADGFLF VVGCDRGKIL FVSESVFKIL NYSQNDLIGQ SLFDYLHPKD
210 220 230 240 250
IAKVKEQLSS SDTAPRERLI DAKTGLPVKT DITPGPSRLC SGARRSFFCR
260 270 280 290 300
MKCNRPSVKV EDKDFPSTCS KKKADRKSFC TIHSTGYLKS WPPTKMGLDE
310 320 330 340 350
DNEPDNEGCN LSCLVAIGRL HSHVVPQPVN GEIRVKSMEY VSRHAIDGKF
360 370 380 390 400
VFVDQRATAI LAYLPQELLG TSCYEYFHQD DIGHLAECHR QVLQTREKIT
410 420 430 440 450
TNCYKFKIKD GSFITLRSRW FSFMNPWTKE VEYIVSTNTV VLANVLEGGD
460 470 480 490 500
PTFPQLTASP HSMDSMLPSG EGGPKRTHPT VPGIPGGTRA GAGKIGRMIA
510 520 530 540 550
EEIMEIHRIR GSSPSSCGSS PLNITSTPPP DASSPGGKKI LNGGTPDIPS
560 570 580 590 600
SGLLSGQAQE NPGYPYSDSS SILGENPHIG IDMIDNDQGS SSPSNDEAAM
610 620
AVIMSLLEAD AGLGGPVDFS DLPWPL
The sequence of this isoform differs from the canonical sequence as follows:
1-47: MADQRMDISSTISDFMSPGPTDLLSSSLGTSGVDCNRKRKGSSTDYQ → MINI
The sequence of this isoform differs from the canonical sequence as follows:
224-224: T → R
225-626: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
274-391: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
278-301: SFCTIHSTGYLKSWPPTKMGLDED → AFCTIHSTGYFGIFTTRTSRHIVL
302-626: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
443-526: ANVLEGGDPT...CGSSPLNITS → SRVDTGHLGQ...QGEPGLGQEK
527-626: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
1-59: MADQRMDISS...MDTDKDDPHG → MSKEAVSLWA...CFYLLLFPPP
Computationally mapped potential isoform sequencesi
There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A669KBF4 | A0A669KBF4_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 630 | Annotation score: | ||
E9PL54 | E9PL54_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 100 | Annotation score: | ||
E9PKG7 | E9PKG7_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 76 | Annotation score: | ||
E9PKN1 | E9PKN1_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 59 | Annotation score: | ||
E9PI92 | E9PI92_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 70 | Annotation score: | ||
E9PNI4 | E9PNI4_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 60 | Annotation score: | ||
E9PRB1 | E9PRB1_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 63 | Annotation score: | ||
A0A669KAX2 | A0A669KAX2_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 86 | Annotation score: | ||
A0A669KB07 | A0A669KB07_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 66 | Annotation score: | ||
E9PSD2 | E9PSD2_HUMAN | Aryl hydrocarbon receptor nuclear t... | ARNTL | 23 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 69 | R → G in AAC51213 (PubMed:9079689).Curated | 1 | |
Sequence conflicti | 123 | K → R in BAA19935 (PubMed:9144434).Curated | 1 | |
Sequence conflicti | 173 | S → P in BAA19939 (PubMed:9144434).Curated | 1 | |
Sequence conflicti | 259 | K → N in BAA19938 (PubMed:9144434).Curated | 1 | |
Sequence conflicti | 264 | D → N in BAA19938 (PubMed:9144434).Curated | 1 | |
Sequence conflicti | 418 | S → N in BAA19937 (PubMed:9144434).Curated | 1 | |
Sequence conflicti | 513 – 514 | SP → LR in AAC51213 (PubMed:9079689).Curated | 2 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_002095 | 1 – 59 | MADQR…DDPHG → MSKEAVSLWALTVSLQPPVP LCVCREMTGSGRRKQQCVTL PFISRELCFYLLLFPPP in isoform MOP3. 1 PublicationAdd BLAST | 59 | |
Alternative sequenceiVSP_002094 | 1 – 47 | MADQR…STDYQ → MINI in isoform BMAL1A and isoform 9. 2 PublicationsAdd BLAST | 47 | |
Alternative sequenceiVSP_002096 | 224 | T → R in isoform BMAL1C. Curated | 1 | |
Alternative sequenceiVSP_002097 | 225 – 626 | Missing in isoform BMAL1C. CuratedAdd BLAST | 402 | |
Alternative sequenceiVSP_002098 | 274 – 391 | Missing in isoform BMAL1D. CuratedAdd BLAST | 118 | |
Alternative sequenceiVSP_035457 | 274 | Missing in isoform 8 and isoform 9. 2 Publications | 1 | |
Alternative sequenceiVSP_002099 | 278 – 301 | SFCTI…GLDED → AFCTIHSTGYFGIFTTRTSR HIVL in isoform BMAL1E. CuratedAdd BLAST | 24 | |
Alternative sequenceiVSP_002100 | 302 – 626 | Missing in isoform BMAL1E. CuratedAdd BLAST | 325 | |
Alternative sequenceiVSP_002101 | 443 – 526 | ANVLE…LNITS → SRVDTGHLGQVERCTVLSRP NSRFLIAGMFTEPTSWKAGT QPSHSSQHPPTAWTACCPLE KVAQRGPTPLFQGFQGEPGL GQEK in isoform BMAL1F. CuratedAdd BLAST | 84 | |
Alternative sequenceiVSP_002102 | 527 – 626 | Missing in isoform BMAL1F. CuratedAdd BLAST | 100 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000389707; ENSP00000374357; ENSG00000133794 [O00327-8] ENST00000401424; ENSP00000385915; ENSG00000133794 [O00327-9] ENST00000403290; ENSP00000384517; ENSG00000133794 ENST00000403482; ENSP00000385897; ENSG00000133794 [O00327-7] ENST00000403510; ENSP00000385581; ENSG00000133794 ENST00000529388; ENSP00000433571; ENSG00000133794 |
GeneIDi | 406 |
KEGGi | hsa:406 |
MANE-Selecti | ENST00000403290.6; ENSP00000384517.1; NM_001297719.2; NP_001284648.1 |
UCSCi | uc001mko.4, human [O00327-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4H10 | X-ray | 2.40 | A | 66-128 | [»] | |
SMRi | O00327 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106899, 99 interactors |
ComplexPortali | CPX-3229, CLOCK-BMAL1 transcription complex |
CORUMi | O00327 |
DIPi | DIP-46008N |
IntActi | O00327, 23 interactors |
MINTi | O00327 |
STRINGi | 9606.ENSP00000384517 |
PTM databases
GlyGeni | O00327, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O00327 |
PhosphoSitePlusi | O00327 |
Genetic variation databases
BioMutai | ARNTL |
Proteomic databases
jPOSTi | O00327 |
MassIVEi | O00327 |
MaxQBi | O00327 |
PaxDbi | O00327 |
PeptideAtlasi | O00327 |
PRIDEi | O00327 |
ProteomicsDBi | 47841 [O00327-2] 47842 [O00327-1] 47843 [O00327-3] 47844 [O00327-4] 47845 [O00327-5] 47846 [O00327-6] 47847 [O00327-7] 47848 [O00327-8] 47849 [O00327-9] |
Protocols and materials databases
Antibodypediai | 11861, 541 antibodies from 44 providers |
DNASUi | 406 |
Genome annotation databases
Ensembli | ENST00000389707; ENSP00000374357; ENSG00000133794 [O00327-8] ENST00000401424; ENSP00000385915; ENSG00000133794 [O00327-9] ENST00000403290; ENSP00000384517; ENSG00000133794 ENST00000403482; ENSP00000385897; ENSG00000133794 [O00327-7] ENST00000403510; ENSP00000385581; ENSG00000133794 ENST00000529388; ENSP00000433571; ENSG00000133794 |
GeneIDi | 406 |
KEGGi | hsa:406 |
MANE-Selecti | ENST00000403290.6; ENSP00000384517.1; NM_001297719.2; NP_001284648.1 |
UCSCi | uc001mko.4, human [O00327-2] |
Organism-specific databases
CTDi | 406 |
DisGeNETi | 406 |
GeneCardsi | ARNTL |
HGNCi | HGNC:701, ARNTL |
HPAi | ENSG00000133794, Low tissue specificity |
MIMi | 602550, gene |
neXtProti | NX_O00327 |
OpenTargetsi | ENSG00000133794 |
PharmGKBi | PA24996 |
VEuPathDBi | HostDB:ENSG00000133794 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3561, Eukaryota |
GeneTreei | ENSGT00940000157523 |
HOGENOMi | CLU_011864_2_2_1 |
InParanoidi | O00327 |
OMAi | YHHEDIP |
OrthoDBi | 331262at2759 |
PhylomeDBi | O00327 |
TreeFami | TF319983 |
Enzyme and pathway databases
PathwayCommonsi | O00327 |
Reactomei | R-HSA-1368108, BMAL1:CLOCK,NPAS2 activates circadian gene expression R-HSA-1989781, PPARA activates gene expression R-HSA-400253, Circadian Clock R-HSA-9707616, Heme signaling |
SignaLinki | O00327 |
SIGNORi | O00327 |
Miscellaneous databases
BioGRID-ORCSi | 406, 9 hits in 1058 CRISPR screens |
ChiTaRSi | ARNTL, human |
GeneWikii | ARNTL |
GenomeRNAii | 406 |
Pharosi | O00327, Tbio |
PROi | PR:O00327 |
RNActi | O00327, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000133794, Expressed in left lobe of thyroid gland and 229 other tissues |
ExpressionAtlasi | O00327, baseline and differential |
Genevisiblei | O00327, HS |
Family and domain databases
CDDi | cd00130, PAS, 2 hits |
Gene3Di | 4.10.280.10, 1 hit |
IDEALi | IID00426 |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR001067, Nuc_translocat IPR001610, PAC IPR000014, PAS IPR035965, PAS-like_dom_sf IPR013767, PAS_fold |
Pfami | View protein in Pfam PF00010, HLH, 1 hit PF00989, PAS, 1 hit |
PRINTSi | PR00785, NCTRNSLOCATR |
SMARTi | View protein in SMART SM00353, HLH, 1 hit SM00086, PAC, 1 hit SM00091, PAS, 2 hits |
SUPFAMi | SSF47459, SSF47459, 1 hit SSF55785, SSF55785, 2 hits |
TIGRFAMsi | TIGR00229, sensory_box, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS50112, PAS, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | BMAL1_HUMAN | |
Accessioni | O00327Primary (citable) accession number: O00327 Secondary accession number(s): A2I2N6 Q99649 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | August 15, 2003 | |
Last modified: | February 23, 2022 | |
This is version 215 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references